Binding of agonists and antagonists to mineralocorticoid receptors in human peripheral mononuclear leucocytes

The binding of agonists (liquorice derivatives) and antagonists (spironolactones and cyproheptadine) to Type I aldosterone binding sites was evaluated in human mononuclear leucocytes and compared with data previously obtained using kidney cytosol or kidney slices from adrenalectomized rats. The affinity of spironolactones (spironolactone and canrenone) is equivalent in all the preparations. In contrast, carbenoxolone and glycyrrhizic acid show no affinity for aldosterone binding sites in mononuclear leucocytes, but bind to receptors in kidney cytosol. The possible explanation of the discrepancies is that, in cytosolic preparations, the two latter compounds may undergo hydrolysis into glycyrrhetinic acid which does possess a measurable affinity for mineralocorticoid receptors in all the preparations.